Intracellular gelation of deoxyhemoglobin S is believed to cause the sickling of SS erythrocytes. We have previously developed an assay using C13/H1 double-magnetic resonance techniques to quantitate the amount of polymer formed in a hemoglobin S gel. We use this technique to study intracellular gelation as a function of oxygen saturation. We found that the amount of polymer formed within SS erythrocytes increased monotonically with decreasing oxygen saturation. Polymer could be detected at oxygen saturations above 90%. This was in excellent agreement with theoretical calculations based on the high intracellular hemoglobin S concentration (34 g/dl) where non-ideality effects must be considered. The curve for polymer formation as a function of oxygen saturation is less sigmoidal than published data for cell sickling; the difference is most apparent for measurements at pH 7.65. These studies indicate that cell sickling and intracellular gelation may represent different cellular phenomena. In addition, measurements of intracellular gelation should be useful in evaluating potential therapeutic agents.